View source for FAM63A

{{Infobox_gene}}
'''Family with sequence similarity 63, member A''' is a [[protein]] that, in humans, is encoded by the '''FAM63A''' [[gene]]. It is located on the minus strand of chromosome 1 at locus 1q21.3.<ref>Gene Cards https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM63A&search=FAM63A</ref>

Evolutionarily, FAM63A [[ortholog]]s are found in most [[vertebrates]], and distant [[homolog]]s of FAM63A are found in [[invertebrates]].<ref>National Center for Bioinformation Technology - BLAST http://blast.ncbi.nlm.nih.gov/Blast.cgi</ref> FAM63A is ubiquitously expressed throughout human tissues, and it is present during every stage of development.<ref>Gene Cards https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM63A&search=FAM63A</ref>

It has been linked to a [[biomarker]] in [[Chronic Kidney Disease]] and [[Alzheimer's Disease]].<ref name = "Köttgen_2010">{{cite journal | vauthors = Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Glazer NL, Parsa A, Gao X, Yang Q, Smith AV, O'Connell JR, Li M, Schmidt H, Tanaka T, Isaacs A, Ketkar S, Hwang SJ, Johnson AD, Dehghan A, Teumer A, Paré G, Atkinson EJ, Zeller T, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Aspelund T, Eiriksdottir G, Launer LJ, Harris TB, Rampersaud E, Mitchell BD, Arking DE, Boerwinkle E, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Haritunians T, Lumley T, Siscovick D, Psaty BM, Zillikens MC, Oostra BA, Feitosa M, Province M, de Andrade M, Turner ST, Schillert A, Ziegler A, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Illig T, Klopp N, Meisinger C, Wichmann HE, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Schreiber S, Aulchenko YS, Felix JF, Rivadeneira F, Uitterlinden AG, Hofman A, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Blankenberg S, Liu Y, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Gudnason V, Shuldiner AR, Coresh J, Schmidt R, Ferrucci L, Shlipak MG, van Duijn CM, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Witteman JC, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS | display-authors = 6 | title = New loci associated with kidney function and chronic kidney disease | journal = Nature Genetics | volume = 42 | issue = 5 | pages = 376–84 | date = May 2010 | pmid = 20383146 | pmc = 2997674 | doi = 10.1038/ng.568 }}</ref>

==Gene==

===Locus===
FAM63A is located on the minus strand of [[chromosome 1]] at band 1q21.3, spanning 11,829 bp. Other genes surrounding FAM63A include ANXA9 and Prune.<ref>Gene Cards https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM63A&search=FAM63A</ref>

===Aliases===
FAM63A has two aliases '''KIAA1390''' and '''PR11-316M1.5'''.<ref>https://www.ncbi.nlm.nih.gov/protein/NP_060849.2</ref>

==mRNA==

=== Primary structure ===
In humans, there are four [[isoforms]] of FAM63A, and there are 10 predicted isoforms. Isoform 1 of FAM63A has a molecular weight of 51.8 [[kilodaltons]], and it contains 11 [[exons]].<ref>National Center for Bioinformation Technology - Protein https://www.ncbi.nlm.nih.gov/protein/?term=FAM63A%20AND%20homo%20sapiens</ref><ref>National Center for Biotechnology Information - AceView - https://www.ncbi.nlm.nih.gov/ieb/research/acembly/av.cgi?db=human&term=FAM63A&submit=Go</ref> The different isoforms tend to differ at the 5' or 3' end by truncation. Transcription produces 23 [[introns]], 14 spliced variants, and 6 unspliced forms.<ref>National Center for Biotechnology Information - AceView - https://www.ncbi.nlm.nih.gov/ieb/research/acembly/av.cgi?db=human&term=FAM63A&submit=Go</ref>

==Protein==
[[File:Multiple Sequence Alignment.png|thumb|right|300px|Multiple sequence alignment of DUF demonstrating conservation across orthologs.  Dark blue indicates complete conservation, pink identical residues, and light blue chemical similarity]]
[[File:Wikipedia Image 3.jpg|thumb|right|200px|This is a 3D depiction of the probable secondary structure of FAM63A.]]

=== Domains and motifs ===
FAM63A contains a [[domain of unknown function]] (DUF 544). DUF544 contains 125 [[amino acids]], running from Met143 to Thr267.<ref>National Center for Bioinformation Technology - BLAST http://blast.ncbi.nlm.nih.gov/Blast.cgi</ref>  Although not completely conserved, this domain is highly conserved across [[vertebrates]], [[invertebrates]], and [[plants]].<ref>San Diego Super Computer http://seqtool.sdsc.edu/CGI/BW.cgi#{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}!</ref>  FAM63A does not contain a [[transmembrane domain]], and it is found primarily in [[cell nucleus|nuclear]] regions of the [[Cell (biology)|cell]].
<ref>PSORT II Prediction http://psort.hgc.jp/form2.html</ref>

Two repeats of four [[glutamine]]s are seen from amino acid 400-403 and from amino acid 426-429, leading to an elevated glutamine composition at the [[C-terminus]].

=== Composition ===
FAM63A is composed of 469 [[amino acid]]s.<ref>San Diego Super Computer - http://seqtool.sdsc.edu/CGI/BW.cgi#{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}!</ref>  There is an increased presence of [[glutamine]] found near the [[C terminus]] making FAM63A glutamine rich.
FAM63A contains a greater amount of negatively charged (acidic) amino acids than positively charged (basic) amino acids which makes FAM63A a slightly acidic protein. Acidic amino acids such as [[aspartic acid]] and [[glutamic acid]] are more prevalent than the basic amino acids such as [[lysine]] and [[arginine]]. This overall acidic composition gives FAM63A an acidic [[isoelectric point]] of 4.6.<ref>San Diego Super Computer - http://seqtool.sdsc.edu/CGI/BW.cgi#{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}!</ref>

=== Post-translational modifications ===
FAM63A contains 25 [[phosphorylation]] sites in humans, including 12 [[serine]], 10 [[threonine]], and 3 [[tyrosine]].  Additionally, there are 5 N-[[myristoylation]] sites, and there is 1 [[prenylation]] site. FAM63A contains no [[glycosylation]] sites, [[transmembrane domains]], or [[signal peptides]].
<ref>ExPASy Bioinformatics Resource Portal http://www.expasy.org/proteomics</ref>
[[File:Wikipedia Image 4.gif|thumb|center|600px|This is a depiction of the posttranslational modifications in FAM63A.]]

=== Secondary structure ===
The [[secondary structure]] for FAM63A has not been explicitly determined. There are, however, predictions for a possible secondary structure. There is a [[coiled-coil domain]] at the end of the protein, and in the predicted secondary structure, there is an [[alpha helix]] between amino acids 410 and 436. This helix is conserved throughout more distant orthologs of FAM63A. These data support each other, and it gives a confident prediction of the secondary structure.<ref>PHYRE2 - http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/9d58a6ea30baa8f6/summary.html</ref>

=== Interacting proteins ===
The following [[genes]] have interactions with '''FAM63A''':  [[GSPT2]], [[NAA38]], [[RNMT]], [[CSNIK1G2]], [[ACOX1]], [[PSMC1]], [[SLC25A37]], [[MMS19]], [[DIAPH1]], [[ME1 (gene)|ME1]], [[GAPDH]], [[UBC]]. 
<ref>Gene Cards https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM63A&search=FAM63A</ref>
After performing a [[yeast two-hybrid]] screen, it was found that [[NAA38]] and FAM63A interact.<ref>STRING - Known and Predicted Protein-Protein Interactions http://string-db.org/newstring_cgi/show_network_section.pl</ref>

== Homology/evolution ==
In FAM63A, there are several [[amino acids]] that are conserved in all [[vertebrates]] for which sequences are available. Gly239 is the only [[amino acid]] that is conserved in all [[vertebrates]], [[invertebrates]], and [[plants]] for which sequences are available. Because there is only one [[amino acid]] that is absolutely conserved, a possible function for the conserved [[Glycine]] was not deduced. The 25 [[amino acid]] sequence ranging from Val313 to Gly338 is the most highly conserved in all [[vertebrates]], [[invertebrates]], and [[plants]] for which sequences are available. Although the sequence is not absolutely conserved, it is very highly conserved, even in the most distantly related organisms like [[fungi]] and [[plants]].

=== Orthologs ===

The [[protein]] FAM63A has several strict [[orthologs]]. These strict orthologs are found in organisms ranging from [[Primates]] to [[Fish]].<ref>National Center for Biotechnology Information - Protein https://www.ncbi.nlm.nih.gov/protein/?term=FAM63A</ref>

{| class="wikitable"
|-
! Scientific Name !! Common Name !! Divergence !! Accession Number !! Length !! Identity !! Similarity !! Query Cover 
|-
| ''[[Homo sapiens]]'' || Humans || N/A || NP_060849.2 || 469 aa || 100%|| 100% || 100% 
|-
| ''[[Pan paniscus]]'' || Bonobo || 6.1 MYA || XP_003817322.1 || 469 aa || 99.1% || 99.4% || 100% 
|-
| ''[[Mus musculus]]'' || House Mouse || 91.0 MYA || NP_955769.1 || 468 aa || 86.0% || 90.2% || 100% 
|-
| ''[[Bos taurus]]'' || Cow || 97.4 MYA || NP_001039389.1 || 469 aa|| 85.6% || 88.5% || 100% 
|-
| ''[[Trichechus manatus latirostris]]'' || West Indian Manatee || 104.7 MYA || XP_004389621.1 || 465 aa || 84.9% || 89.8% || 100% 
|-
| ''[[Sarcophilus harrisii]]'' || Tasmanian Devil || 176.1 MYA || XP_003769968.1 || 464 aa || 78.3% || 82.9% || 100% 
|-
| ''[[Taeniopygia guttata]]'' || Zebra Finch|| 324.0 MYA || XP_002191502.2 || 335 aa || 43.2% || 80.1% || 53% 
|-
| ''[[Gallus gallus]]'' || Chicken || 324.5 MYA || XP_003642724 || 462 aa || 66.9% || 76.1% || 92% 
|-
| ''[[Chrysemys picta bellii]]'' || Painted Turtle || 324.5 MYA || XP_005293753.1 || 525 aa || 62.0%|| 87.2% || 78% 
|-
|''[[Pelodiscus sinensis]]''|| Chinese Softshell Turtle || 324.5 MYA|| XP_006119467.1 || 502 aa || 61.6% || 77.4% || 94% 
|-
| ''[[Alligator mississippiensis]]'' || American Alligator || 324.5 MYA || XP_006274676.1 || 520 aa || 59.90% || 77.50% || 86% 
|-
| ''[[Pseudopodoces humilis]]'' || Ground Tit || 324.5 MYA || XP_005533539.1 || 502 aa || 58.0% || 82.3% || 78% 
|-
| ''[[Anas platyrhynchos]]'' || Mallard || 324.5 MYA || XP_005026841.1 || 415 aa || 57.9% || 78.6% || 83% 
|-
| ''[[Xenopus tropicalis]]'' || Western Clawed Frog || 361.2 MYA || XP_002937311.1 || 506 aa || 61.3% || 83.7% || 76% 
|-
| ''[[Latimeria chalumnae]]'' || West Indian Ocean Coelacanth || 430.0 MYA || XP_006006147.1 || 513 aa || 44.7% || 86.9% || 55% 
|-
| ''[[Danio rerio]]'' || Zebrafish || 454.6 MYA || XP_005159508.1 || 520 aa || 52.2% || 80.2% || 76% 
|}

FAM63A evolved through time at a relatively moderate rate.
[[File:Wikipedia Image 1.jpg|thumb|700px|center|This shows the protein conservation throughout evolution. FAM63A evolved at a medium rate compared with cytochrome c (fast) and fibrinogen (slow).]]

=== Paralogs ===

The [[protein]] '''FAM63A''' has only one known [[paralog]]: '''FAM63B'''.  FAM63B is predicted as having a molecular function in the cell.<ref>Gene Cards https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM63B</ref>  All of the [[vertebrates]] for which sequences are available have two copies of the FAM63 gene, both A and B. '''FAM63A''' and '''FAM63B''' likely split apart around 666 million years ago, as the closest relative to ''[[Homo sapiens]]'' containing only one FAM63 is a [[tapeworm]], which diverged 666 million years ago.<ref>National Center for Biotechnology Information - Protein https://www.ncbi.nlm.nih.gov/protein/?term=FAM63A</ref>
 
{| class="wikitable"
|-
! Sequence Number !! Scientific Name !! Common Name !! Divergence !! Accession Number !! Length !! Identity !! Similarity !! Query Cover !! E-value
|-
| protein FAM63B isoform a || ''[[Homo sapiens]]'' || Human || N/A || NP_001035540.1 || 621 aa || 41.9% || 76.7% || 68% || 2.00E-129
|}

==Expression==

===Promoter===
The promoter region contains a number of [[transcription factors]].<ref>Genomatrix - ElDorado - Promoter and transcription factors for FAM63A. http://www.genomatix.de/?s=23e6b2edc9ca33fe998f299bafe56b99</ref>  Those with high scores include estrogen response elements, TATA boxes, glucocoticoid response elements, and Ccaat/enchancer binding proteins.  Experimental data reveals that FAM63A expression decreases when the [[estrogen receptor]] is not present, suggesting that the estrogen response elements may serve as an important promoter regulatory mechanism for this protein.<ref>Estrogen receptor alpha-silenced MCF7 breast cancer cells. Profile: GDS4061/ FAM63A. ncbi.nlm.nih.gov/geo/tools/profiles</ref>

===Protein expression===
FAM63A is a protein that is ubiquitously expressed across human tissues and throughout development. Although FAM63A is expressed ubiquitously, there are certain tissues that have higher levels of expression including the [[heart]], [[thyroid]], [[ganglia]], and [[blood]].<ref>National Center for Biotechnology Information - GEO Profiles https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:221856_s_at</ref>

[[File:Wikipedia Image 5.jpg|thumb|center|700px|This is a depiction of the expression levels of FAM63A throughout different human tissues.]]

== Clinical significance ==

Although there is no specific function determined for FAM63A, there are a few researchers who have discovered possible functions. It has been postulated that FAM63A may be associated with [[renal function]] and [[Chronic Kidney Disease]].<ref name = "Köttgen_2010" />

Figgins, Minster, and Demirci examined 17,343 functional [[single nucleotide polymorphisms]], demonstrating a strong association between [[Alzheimer's Disease]] duration and FAM63A.<ref>{{cite journal | vauthors = Figgins JA, Minster RL, Demirci FY, Dekosky ST, Kamboh MI | title = Association studies of 22 candidate SNPs with late-onset Alzheimer's disease | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 150B | issue = 4 | pages = 520–6 | date = June 2009 | pmid = 18780302 | pmc = 2751631 | doi = 10.1002/ajmg.b.30851 }}</ref>  Another gene located on 1q21, [[Cathepsin S|CTSS]], was also strongly associated with disease duration, the authors believe that there is a strong [[linkage disequilibrium]] between the two genes.  FAM63A was identified as one of 39 genes exclusively expressed in CML cells, grouped with four other genes believed to function in [[protein ligation]].

== References ==
{{reflist|33em}}